The microchips for DNA sample processing and DNA-base sequence analysis are already commercialized. In this micro total analysis system, it is necessary to provide a driving system that drives the DNA sample or the biochemical reagent to flow along the microchannel inside the biochip. In designing the driving system, how to avoid pollution between the sample, the reagent and the driving system, is one of the major problems.
In designing the driving system of a biochip, three approaches may be selected. They are on-chip mechanical micropump, the on-chip electro-kinetic micropump and the external servo system.
1. The on-chip mechanical micropump
An on-chip mechanical micropump may be prepared directly by the micro-machining technology. If this approach is adopted, a moveable part shall be provided inside the microchannel of the chip. The "electrostatically driven diaphragm micropump" designed by Roland Zengerle et al. in their U.S. Pat. No. 5,529,465 is a good example.
In the Zengerle invention, the micropump includes a pressure chamber. A reciprocal pumping power is generated by electrostatics. With the help of two passive check valve, microflows are driven with a 350 .mu.l/min working velocity.
A simplified "micromachined peristaltic pump" was disclosed by Frank T. Hartley in his U.S. Pat. No. 5,705,018. In this invention, a series of block flexible conductive strips are positioned in the internal wall of a microchannel. When a voltage pulse passes along the microchannel, the flexible conductive strips are uplifted in sequence by the electrostatics so generated, such that a peristaltic movement is generated. This peristaltic movement drives the microflow along the microchannel. In the Hartley invention, the working velocity is about 100 .mu.l/min.
The on-chip mechanical micropump does not provide the function such that the chip may be repeatedly used for different samples. This is because a microchannel with moveable parts is difficult to clean up residual samples or biochemical reagents after the reaction. Another problem is that the on-chip mechanical micropump, especially the peristaltic pump, involves expensive material costs. These biochips are not suited for disposable applications.
2. The on-chip electro-kinetic micropump
The on-chip electro-kinetic micropump is a non-mechanical micropump. Inside the pump there are no moveable members. The driving force is generated by electro osmosis (EO), electro hydrodynamics (EHD) or electro phorosis (EP).
In 1997, Peter J. Zanzucchi et al. disclosed an "apparatus and method for controlling fluid flow in microchannels in their U.S. Pat. No. 5,632,876. In this invention the driving force of the microflow is a combination of electro-osmosis and electro-hydrodynamics.
The microfluid is driven by the EHD force and the EO force to proceed, retreat or pause. In using the EO force, the fluid shall be a polar solution. On the other hand, when the EHD force is used, the fluid shall be a non-polar solution, such as an organic solution. In this patent, Zanzucchi claimed that both polar and non-polar solutions are applicable in his invention, when necessary integration of the two forces are made.
In 1997 Paul C. H. Li and D. Jed Harrison published an article: "Transport, manipulation and reaction of biological cells on-chip using electrokinetic effects" in Anal. Chem., 1997, 69, 1564-1568. This article disclosed a microflow driving system using the combination of the EO force and the EP force. Due to the differences between the EP force and EO force in different channels and areas, the biochemical samples may be driven and even classified. However, no matter which force is the case, objects driven by the force are the electric particles in the solution, not the solution itself.
Although the on-chip electro-kinetic micropump is easy to prepared and its cost is low, there are several limitations. First, in the application, the microchannel(s) shall be filled with solutions in advance. It is not possible to introduce the sample or reagent into the channel before filling the channel with solutions. Secondly, an electro-kinetic micropump can only move a fluid to a limited distance. Its working velocity is about 10 .mu.l/min. It is necessary to apply a bias of hundreds or even thousands volt within a very short distance. The operation cost is relatively high. Last but not least, the EHD pump can only apply to non-polar organic solutions and the EO pump and the EP pump may only apply to polar solutions where density of ion influences the driving efficiency of the pump. As a result, if a sample or reagent with complicated components is introduced, or if density of ion varies during the reaction, problems will occur in the flow driving system.
3. The external servo system
To use an external servo system to drive a microflow may be the simplest idea. If most moveable members are removed to outside of the microchannel, the structure of the microchannel must be simplified and the manufacture cost may be saved. This approach is obviously applicable to disposable biochips.
In designing an external servo system, one of the most important questions is how the "world-to-chip" interface may be designed such that the driving force may be connected to the fluid channel under miniature scales. If this problem may be solved, a simplified, low cost and disposable biochip, with no moveable member in the microchannel, may be obtained.
It is thus a need in the industry to provide an apparatus and a method for driving a microflow wherein the driving force is provided by an external driving device.
It is also a need in the industry to provide an apparatus for driving a microflow where no moveable member is required in the fluid channel for the microflow.
It is also a need in the industry to provide an apparatus for driving a microflow with lower manufacture costs.
It is also a need in the industry to provide an apparatus for driving a microflow with a simplified world-to-chip interface.